This proposal is designed to localize discrete regions of the brain which interact with a radioactive form of the tricyclic antidepressant imipramine in an effort to localize the sites of action of this compound. Definitive experiments will be performed to demonstrate that some of these sites reside presynaptically on serotonergic neurons. This study will demonstrate specifically how serotonin receptors are affected by chronic imipramine treatment, which serotonin receptor subtype (5HT-1 or 5HT-2) is affected and where this effect is taking place. This study will also demonstrate where and how lithium (an ion effective in preventing recurrent episodes of mania and depression in manic depressive illness) is affecting the serotonin receptor subtypes in an attempt to correlate regions of overlap with regions affected by imipramine. Ultimately, the goal is to define nuclei in the brain which may be responsible for depressive illness and to provide further insight into the mechanism of action of antidepressants.